Study to Uncover Pathways to Exceptional Cognitive Resilience in Aging (SUPERAging)

PROJECT SUMMARY (Overall): The primary goal is to establish a multicenter SuperAging Consortium to identify behavioral, health, biologic, genetic, environmental, socioeconomic, psychosocial, anatomic and neuropathologic factors associated with SuperAging. These goals will be achieved through an organizational structure with 3 Cores

(Administrative/Biostatistics, Clinical/Imaging, and Biospecimen/Neuropathology) and 2 Research Projects. The Consortium will enroll 500 participants across 4 US Sites located in Illinois, Wisconsin, Michigan and Georgia, and the Canadian Site in Southwest, Ontario, with a focus on the enrollment of Black SuperAgers and Cognitively

Average Elderly Controls with similar demographics (Controls). The Administrative/Biostatistics Core will provide governance and fiscal oversight, maintain scientific integrity, and create a centralized biostatistics and database infrastructure to harmonize the goals and activities of the Cores, Sites, and Projects, with each other,

with the NIA and with extramural collaborators. The Clinical/Imaging Core will standardize criteria for the uniform cross-site and multidisciplinary characterization of SuperAgers, streamline recruitment including that of Black participants, enter relevant information in the comprehensive database, support co-enrollment into Project

1, and encourage collaborative ventures aiming to understand the factors that promote SuperAging. The Biospecimen/Neuropathology Core will collect and bank brain tissue and blood products from SuperAging and Control cases, according to optimized procedures. It will render pathological diagnoses, quantitate selected

markers of neurodegeneration and neuronal structure, coordinate the analyses of plasma biomarkers for Alzheimer's disease, and make specimens available for collaborative investigations. Project 1 will use state-of- the-art wearable technology to obtain real-time measurements in the course of everyday life to characterize

quantitative parameters related to sleep, physical activity, autonomic responsivity, and social engagement to determine whether SuperAgers have relatively preserved and quantitatively determined physiologic and behavioral `complexity' compared to Controls. Project 2 will use transcriptomic, genetic, and protein profiling

approaches to test the hypothesis that SuperAgers will demonstrate significant molecular differences in their central and peripheral immune and inflammatory system parameters compared to matched Control and Alzheimer's disease participants. By identifying neurobiologic features that contribute to superior memory

performance in old age, outcomes from this Consortium will help isolate factors that promote successful cognitive aging and perhaps also prevent age-related brain diseases such as Alzheimer's disease.